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nemo-like kinase is an essential co-activator of Wnt signaling during early zebrafish development
- Source :
- Development. 131:2899-2909
- Publication Year :
- 2004
- Publisher :
- The Company of Biologists, 2004.
-
Abstract
- Wnt/β-catenin signaling regulates many aspects of early vertebrate development, including patterning of the mesoderm and neurectoderm during gastrulation. In zebrafish, Wnt signaling overcomes basal repression in the prospective caudal neurectoderm by Tcf homologs that act as inhibitors of Wnt target genes. The vertebrate homolog of Drosophila nemo, nemo-like kinase (Nlk), can phosphorylate Tcf/Lef proteins and inhibit the DNA-binding ability of β-catenin/Tcf complexes, thereby blocking activation of Wnt targets. By contrast, mutations in a C. eleganshomolog show that Nlk is required to activate Wnt targets that are constitutively repressed by Tcf. We show that overexpressed zebrafish nlk, in concert with wnt8, can downregulate two tcf3 homologs, tcf3a and tcf3b, that repress Wnt targets during neurectodermal patterning. Inhibition of nlk using morpholino oligos reveals essential roles in regulating ventrolateral mesoderm formation in conjunction with wnt8, and in patterning of the midbrain, possibly functioning with wnt8b. In both instances, nlk appears to function as a positive regulator of Wnt signaling. Additionally, nlk strongly enhances convergent/extension phenotypes associated with wnt11/silberblick, suggesting a role in modulating cell movements as well as cell fate.
- Subjects :
- Mesoderm
Embryo, Nonmammalian
animal structures
Molecular Sequence Data
Biology
Cell fate determination
TCF/LEF family
Nervous System
Polymerase Chain Reaction
Gene Expression Regulation, Enzymologic
Proto-Oncogene Proteins
Ectoderm
Morphogenesis
medicine
Animals
Amino Acid Sequence
Molecular Biology
Zebrafish
Conserved Sequence
In Situ Hybridization
Body Patterning
Sequence Homology, Amino Acid
Wnt signaling pathway
Brain
Gene Expression Regulation, Developmental
LRP5
Gastrula
Zebrafish Proteins
biology.organism_classification
Wnt Proteins
medicine.anatomical_structure
TCF3
embryonic structures
Mesoderm formation
Cancer research
Mitogen-Activated Protein Kinases
Sequence Alignment
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....9ec5551a39450f77b07378c10eee9384